The pragmatic studies in this proposal will include biological dosimetry to determine RBE's for p(42) + Be and P(48) + Be neutron beams from the University of Washington Scanditronix Clinical Neutron Therapy System relative to d (22) + Be neutrons currently used for neutron therapy and to 137Cs gamma rays. Two in vivo systems (mouse skin, mouse intestinal crypt cell survival assay by histologic microcolony techniques) and the V-79 cells in vitro will be used. V-79 cell survival as function of position in various sized collimated fields, field position across the neutron beam, and depth in tissue equivalent material will be determined for p(48) + Be neutrons. This will be correlated with physical measurements of neutron energy distribution and gamma contamination. More basic studies with p(48) + Be neutrons will attempt to provide biological rationale for ongoing or new patient treatment protocols. Patterns of sublethal damage repair and potentially lethal damage repair and their interaction in EMT-6 cells will be investigated in split-dose studies with n-n and n-gamma combinations. As a followup to promising results using neutron + photons in preoperative radiation of human transitional cell carcinoma, patterns of sublethal and potentially lethal damage repair will be investigated in human TCC lines irradiated in vitro with neutrons or gamma rays. The ability of WR-2721 and related-SH containing radioprotectors to protect acutely responding (bone marrow, gut) and late responding normal tissue (kidney, vascular elements in spinal cord) against neutrons will be investigated. The long term goal is to provide a rationale biologial basis for the selective application of neutrons to the treatment of human cancer.